Adiponectin is a type of protein secreted from adipocytes. Normal adipocytes secrete adiponectin and are sensitive to insulin. In obese patients adipocytes can accumulate adipose and become hypertrophied, which results in the decreased secretion of adiponectin. Decreased adiponectin secretion leads to the increased secretion of TNF-α and resistin, which can cause insulin resistance. This leads to diseases such as metabolic syndrome, diabetes, hypertension, hyperlipidemia, obesity, or arteriosclerosis. Therefore, increases in adiponectin secretion from adipocytes can prevent and ameliorate diseases, such as metabolic syndrome, diabetes, hypertension, hyperlipidemia, obesity or arteriosclerosis.
The mechanism of the adiponectin secretion from adipocytes has yet to be explained. Qiang, et al. (Molecular and Cellular Biology, 2007, 27 4698-4707) recites that activities of Ero1-Lα, an endoplasmic reticulum oxidoreductase, and modulators of peroxisome proliferator-activated receptor γ (PPARγ), and SIRT1, an NAD-dependent deacetylation enzyme, control the secretion of adiponectin in 3T3-L1 adipocytes. In addition, it has been reported that insulin tolerance disorders can be treated or prevented by increasing protein levels and activities of sirtuins, such as SIRT1 (published Japanese Translation No. 2007-527418 of PCT international Publication WO2005065667A3).
Nicotinamide mononucleotide (NMN) is an intermediate metabolite from synthesis of the coenzyme NAD+. In recent years, NMN has been reported to have an ameliorative effect on secretory ability of insulin in aged mice, a dramatic enhancement of insulin sensitivity and secretion in high fat diet and aging induced type 2 diabetes in mice (U.S. Pat. No. 7,737,158), and a remarkable enhancement of mitochondrial function in aged muscle. Moreover, it is reported that administration of NMN is useful in improving and preventing the symptoms of various age-related diseases, such as obesity, increased serum lipid levels, decreased insulin sensitivity, memory decline, and deterioration of optical function, such as macular degeneration (WO 2014/146044).